{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T03:37:57Z","timestamp":1782185877473,"version":"3.54.5"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T00:00:00Z","timestamp":1425945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0118906","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T17:48:26Z","timestamp":1426009706000},"page":"e0118906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Changes in Protein Expression in Two Cholangiocarcinoma Cell Lines Undergoing Formation of Multicellular Tumor Spheroids In Vitro"],"prefix":"10.1371","volume":"10","author":[{"given":"Carlo","family":"Mischiati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blendi","family":"Ura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Roncoroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Elli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cervellati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Squerzanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Doneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Polverino de Laureto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"de Franceschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Calza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Barrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Merali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Bergamini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Agostinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1083\/jcb.109.4.1495","article-title":"Rearrangements of desmosomal and cytoskeletal proteins during the transition from epithelial to fibroblastoid organization in cultured rat bladder carcinoma cells","volume":"109","author":"B Boyer","year":"1989","journal-title":"J Cell Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial-mesenchymal transition","volume":"119","author":"R Kalluri","year":"2009","journal-title":"J Clin Invest"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.bbapap.2009.05.001","article-title":"Towards understanding epithelial-mesenchymal transition: a proteomics perspective","volume":"1794","author":"RA Mathias","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1158\/0008-5472.CAN-12-1223","article-title":"Microenvironmental regulation of epithelial-mesenchymal transitions in cancer","volume":"72","author":"D Gao","year":"2012","journal-title":"Cancer Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.radonc.2011.05.066","article-title":"Expression of E-cadherin and vimentin correlates with metastasis formation in head and neck squamous cell carcinoma patients","volume":"99","author":"MM Nijkamp","year":"2011","journal-title":"Radiother Oncol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"9192","DOI":"10.1158\/0008-5472.CAN-09-1257","article-title":"Epithelial-to-mesenchymal transition and ovarian tumor progression induced by tissue transglutaminase","volume":"69","author":"M Shao","year":"2009","journal-title":"Cancer Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1158\/0008-5472.CAN-08-0364","article-title":"Identification and characterization of ovarian cancer-initiating cells from primary human tumours","volume":"68","author":"S Zhang","year":"2008","journal-title":"Cancer Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.oraloncology.2012.10.009","article-title":"Epithelial to mesenchymal transition in head and neck squamous cell carcinoma","volume":"49","author":"A Smith","year":"2013","journal-title":"Oral Oncol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s10585-009-9242-2","article-title":"Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature","volume":"26","author":"GJ Klarmann","year":"2009","journal-title":"Clin Exp Metastasis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/jcp.21223","article-title":"Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression","volume":"213","author":"H Hugo","year":"2007","journal-title":"J Cell Physiol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.semcancer.2005.05.002","article-title":"Three-dimensional tissue culture models in cancer biology","volume":"15","author":"JB Kim","year":"2005","journal-title":"Semin Cancer Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e75345","DOI":"10.1371\/journal.pone.0075345","article-title":"A 3D fibrous scaffold inducing tumoroids: a platform for anticancer drug development","volume":"8","author":"YK1 Girard","year":"2013","journal-title":"PLoS One"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1021\/pr2012472","article-title":"Characterization of changes in the proteome in different regions of 3D multicell tumor spheroids","volume":"11","author":"KM1 McMahon","year":"2012","journal-title":"J Proteome Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e77497","DOI":"10.1371\/journal.pone.0077497","article-title":"Hypoxia Promotes Epithelial\u2014Mesenchymal Transition of Hepatocellular Carcinoma Cells via Inducing GLIPR-2 Expression","volume":"8","author":"SG Huang","year":"2013","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.bbamcr.2014.01.013","article-title":"GPI\/AMF inhibition blocks the development of the metastatic phenotype of mature multi-cellular tumor spheroids","volume":"1843","author":"JC Gallardo-P\u00e9rez","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1038\/bjc.2011.452","article-title":"E\/N-cadherin switch mediates cancer progression via TGF-\u03b2-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma","volume":"105","author":"K Araki","year":"2011","journal-title":"Br J Cancer"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/S0140-6736(05)67530-7","article-title":"Cholangiocarcinoma","volume":"366","author":"SA Khan","year":"2005","journal-title":"Lancet"},{"key":"ref18","first-page":"579","article-title":"Biliary adenocarcinoma. Characterisation of three new human tumor cell lines","volume":"1","author":"A Knuth","year":"1985","journal-title":"J Hepatol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1111\/j.1478-3231.2008.01749.x","article-title":"Resveratrol inhibits cell growth in a human cholangiocarcinoma cell line","volume":"28","author":"L Roncoroni","year":"2008","journal-title":"Liver Int"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s10555-011-9344-6","article-title":"EMT in carcinoma progression and dissemination: Facts, unanswered questions, and clinical considerations","volume":"31","author":"J Bastid","year":"2012","journal-title":"Cancer Metastasis Rev"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"MM Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.3892\/mmr.2013.1375","article-title":"Comparative proteomic analysis of ductal breast carcinoma demonstrates an altered expression of chaperonins and cytoskeletal proteins","volume":"7","author":"P Carcoforo","year":"2013","journal-title":"Mol Med Rep"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e68376","DOI":"10.1371\/journal.pone.0068376","article-title":"HIV-1 Vpr modulates macrophage metabolic pathways: a SILAC-based quantitative analysis","volume":"8","author":"CA Barrero","year":"2013","journal-title":"PLoS One"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"UK Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1007\/s00726-011-0963-6","article-title":"Effects of the regulatory ligands calcium and GTP on the thermal stability of tissue transglutaminase","volume":"42","author":"C Cervellati","year":"2012","journal-title":"Amino Acids"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/9781118105771.ch1","article-title":"Structure and regulation of type 2 transglutaminase in relation to its physiological functions and pathological roles","volume":"78","author":"CM Bergamini","year":"2011","journal-title":"Adv Enzymol Relat Areas Mol Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1432-1033.1973.tb02969.x","article-title":"Pyruvate kinase. Classes of regulatory isoenzymes in mammalian tissues","volume":"37","author":"J Carbonell","year":"1973","journal-title":"Eur J Biochem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1016\/S0021-9258(18)93993-1","article-title":"Comparative properties of yeast and muscle aldolase","volume":"236","author":"OC Richards","year":"1961","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/0076-6879(69)13024-4","article-title":"Cytoplasmic and mitochondrial malate dehydrogenases from beef kidney","volume":"13","author":"D Dupourque","year":"1969","journal-title":"Methods Enzymol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/0076-6879(69)13011-6","article-title":"Isocitrate dehydrogenase (TPN specific) from pig heart","volume":"13","author":"WW Cleland","year":"1969","journal-title":"Methods Enzymol"},{"key":"ref31","first-page":"23","article-title":"E-cadherin\u2019s dark side: possible role in tumor progression","volume":"1826","author":"FJ Rodriguez","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1096\/fj.06-7598com","article-title":"Identification of two GTP-independent alternatively spliced forms of tissue transglutaminase in human leukocytes, vascular smooth muscle, and endothelial cells","volume":"21","author":"TS Lai","year":"2007","journal-title":"FASEB J"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1007\/s00018-012-1122-2","article-title":"EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness","volume":"69","author":"E S\u00e1nchez-Till\u00f3","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI36183","article-title":"Biomarkers for epithelial-mesenchymal transitions","volume":"119","author":"M Zeisberg","journal-title":"J Clin Invest"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"446","DOI":"10.18632\/oncotarget.872","article-title":"The Paradox of E-Cadherin: Role in response to hypoxia in the tumor microenvironment and regulation of energy metabolism","volume":"4","author":"K Chu","year":"2013","journal-title":"Oncotarget"},{"key":"ref36","first-page":"75","article-title":"Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic","volume":"1796","author":"A Voulgari","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/S0140-6736(13)61903-0","article-title":"Cholangiocarcinoma","volume":"383","author":"N Razumilava","year":"2014","journal-title":"Lancet"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1245\/s10434-010-0925-3","article-title":"Epithelial-mesenchymal transition induced by hepatitis C virus core protein in cholangiocarcinoma","volume":"17","author":"T Li","year":"2010","journal-title":"Ann Surg Oncol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"573","DOI":"10.3892\/ijo.2012.1499","article-title":"Angiotensin II enhances epithelial-to-mesenchymal transition through the interaction between activated hepatic stellate cells and the stromal cell-derived factor-1\/CXCR4 axis in intrahepatic cholangiocarcinoma","volume":"41","author":"K Okamoto","year":"2012","journal-title":"Int J Oncol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/1087057104265040","article-title":"The use of 3-D cultures for high-throughput screening: the multicellular spheroid model","volume":"9","author":"LA Kunz-Schughart","year":"2004","journal-title":"J Biomol Screen"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.bbrc.2014.11.007","article-title":"TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin","volume":"455","author":"X Yao","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"6920","DOI":"10.1038\/onc.2008.343","article-title":"Cadherins and cancer: how does cadherin dysfunction promote tumor progression?","volume":"27","author":"A Jeanes","year":"2008","journal-title":"Oncogene"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1158\/0008-5472.CAN-07-2938","article-title":"Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways","volume":"68","author":"TT Onder","year":"2008","journal-title":"Cancer Res"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"6065","DOI":"10.1210\/en.2008-0687","article-title":"Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal","volume":"149","author":"B Sen","year":"2008","journal-title":"Endocrinology"},{"key":"ref45","first-page":"3149","article-title":"Activation of \u03b2-catenin stimulated by mechanical strain and estrogen requires estrogen receptor in mesenchymal stem cells (MSCs)","volume":"18","author":"XL Yao","year":"2014","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1136\/jclinpath-2013-201806","article-title":"Epithelial-mesenchymal transition phenotypes are associated with patient survival in intrahepatic cholangiocarcinoma","volume":"67","author":"MJ Gu","year":"2014","journal-title":"J Clin Pathol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/cphy.c120027","article-title":"Bile formation and secretion","volume":"3","author":"JL Boyer","year":"2013","journal-title":"Compr Physiol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"RA Cairns","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.clinbiochem.2012.04.004","article-title":"Proteomics-based identification of \u03b1-enolase as a potential prognostic marker in cholangiocarcinoma","volume":"45","author":"P Yonglitthipagon","year":"2012","journal-title":"Clin Biochem"},{"issue":"13 Suppl","key":"ref50","first-page":"115","article-title":"Cytokines released from activated human macrophages induce epithelial mesenchymal transition markers of cholangiocarcinoma cells","author":"A Techasen","year":"2012","journal-title":"Asian Pac J Cancer Prev"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e57971","DOI":"10.1371\/journal.pone.0057971","article-title":"Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel","volume":"8","author":"M Bayet-Robert","year":"2013","journal-title":"PLoS One"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nm0311-291","article-title":"Metabolism unhinged: IDH mutations in cancer","volume":"17","author":"JR Prensner","year":"2011","journal-title":"Nat Med"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/MOG.0000000000000050","article-title":"Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma","volume":"30","author":"AR Grassian","year":"2014","journal-title":"Curr Opin Gastroenterol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00726-011-1167-9","article-title":"Tissue transglutaminase: a new target to reverse cancer drug resistance","volume":"44","author":"A Budillon","year":"2013","journal-title":"Amino Acids"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1182\/blood-2011-09-377598","article-title":"Calcium blockers decrease the bortezomib resistance in mantle cell lymphoma via manipulation of tissue transglutaminase activities","volume":"119","author":"HJ Jung","year":"2012","journal-title":"Blood"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0118906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T21:09:18Z","timestamp":1651439358000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0118906"}},"subtitle":[],"editor":[{"given":"Mitchell","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,10]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0118906","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,10]]}}}